Developmental trajectories of GABAergic cortical interneurons are sequentially modulated by dynamic <i>FoxG1</i> expression levels.

Abstract

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of <i>FoxG1</i> expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in <i>FoxG1</i> expression levels during interneuron specification and migration. Our findings underscore the gene dosage-dependent function of <i>FoxG1</i>, aligning with clinical observations of <i>FOXG1</i> haploinsufficiency and duplication in syndromic forms of autism spectrum disorders. In conclusion, our results reveal the finely tuned developmental clock governing cortical interneuron development, driven by temporal dynamics and the dose-dependent actions of <i>FoxG1</i>.